Maria Ciofani
Associate Professor of Immunology
Transcriptional Regulation of Proinflammatory Lymphocytes
IL-17-expressing CD4 T helper (Th17) cells are important members of the intestinal immune cell community that contribute to protection against bacterial and fungal infections, and maintenance of intestinal homeostasis. Although central to immunity, dysregulted Th17 cell function has been implicated in tissue inflammation and autoimmune disease (e.g. Inflammatory bowel disease, arthritis, and multiple sclerosis). In order to understand this balance between healthy and pathogenic responses, we are interested in defining the transcriptional regulatory mechanisms that govern (1) Th17 cell specification from naive T cell precursors and, (2) Th17 cell effector plasticity during inflammation. Combining genome-wide interrogation of regulatory information (transcription factor occupancy, chromatin accessibility, and transcriptional output) with gene-deficiency models in mice, we can dissect the contribution of key transcriptional regulators in proinflammatory T cell function.
We currently have open positions for students, postdoctoral fellows and a research technician.
Current Appointments & Affiliations
- Associate Professor of Immunology, Immunology, Basic Science Departments 2020
- Member of the Duke Cancer Institute, Duke Cancer Institute, Institutes and Centers 2013
Contact Information
- 128 Jones Bldg, 207 Researchr, 3010 DUMC, Durham, NC 27710
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maria.ciofani@duke.edu
(919) 684-1166
- Background
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Education, Training, & Certifications
- Ph.D., University of Toronto (Canada) 2007
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Duke Appointment History
- Assistant Professor of Immunology, Immunology, Basic Science Departments 2013 - 2020
- Recognition
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In the News
- Expertise
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Subject Headings
- Animals
- Antigens, CD4
- Autoimmune Diseases
- Autoimmunity
- Basic-Leucine Zipper Transcription Factors
- Bone Marrow Cells
- CD4-Positive T-Lymphocytes
- CD8-Positive T-Lymphocytes
- Cell Aging
- Cell Cycle
- Cell Death
- Cell Differentiation
- Cell Division
- Cell Line
- Cell Lineage
- Cell Survival
- Cells, Cultured
- Chromatin Immunoprecipitation
- Cloning, Molecular
- Coculture Techniques
- Cytokines
- Cytotoxicity Tests, Immunologic
- DEAD-box RNA Helicases
- DNA Mutational Analysis
- DNA-Binding Proteins
- Developmental Biology
- Disease Models, Animal
- Drosophila
- Drosophila Proteins
- Early Growth Response Protein 1
- Encephalomyelitis, Autoimmune, Experimental
- Enhancer Elements, Genetic
- Enzyme Activation
- Epigenesis, Genetic
- Epitopes
- Extracellular Signal-Regulated MAP Kinases
- Female
- Fetus
- Flow Cytometry
- Fluorescent Antibody Technique
- Fos-Related Antigen-2
- Gene Deletion
- Gene Expression Profiling
- Gene Expression Regulation
- Gene Expression Regulation, Leukemic
- Gene Library
- Gene Rearrangement
- Gene Regulatory Networks
- Genome-Wide Association Study
- Hematopoietic Stem Cells
- Hepatocytes
- Humans
- Immunomodulation
- Inhibitor of Apoptosis Proteins
- Inhibitor of Differentiation Proteins
- Interferon Regulatory Factors
- Intracellular Signaling Peptides and Proteins
- Kinetics
- Leukemia, T-Cell
- Ligands
- Lymphocyte Activation
- Lymphoid Progenitor Cells
- Lymphopoiesis
- Membrane Proteins
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Mice, Mutant Strains
- Mice, Transgenic
- MicroRNAs
- Microtubule-Associated Proteins
- Models, Genetic
- Molecular Sequence Data
- Mutation
- Neoplasm Proteins
- Nuclear Receptor Subfamily 1, Group F, Member 3
- Organ Culture Techniques
- PTEN Phosphohydrolase
- Phosphatidylinositol 3-Kinases
- Phosphorylation
- Pregnancy
- Protein Isoforms
- Protein Precursors
- Proto-Oncogene Proteins c-akt
- RGS Proteins
- RNA Precursors
- RNA Processing, Post-Transcriptional
- Receptor, Notch1
- Receptors, Antigen, T-Cell
- Receptors, Antigen, T-Cell, alpha-beta
- Receptors, Antigen, T-Cell, gamma-delta
- Receptors, Notch
- Regulatory Elements, Transcriptional
- Reverse Transcriptase Polymerase Chain Reaction
- Ribonuclease III
- Sequence Analysis, RNA
- Signal Transduction
- Stem Cells
- Stromal Cells
- Systems Biology
- T-Lymphocyte Subsets
- T-Lymphocytes
- T-Lymphocytes, Helper-Inducer
- Th17 Cells
- Thymus Gland
- Transcription Factor AP-1
- Transcription Factors
- Transcription, Genetic
- Transcriptional Activation
- Transgenes
- Tumor Suppressor Protein p53
- Research
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Selected Grants
- Basic Immunology Training Program awarded by National Institutes of Health 2002 - 2025
- Regulatory mechanisms governing Th17 cell effector identity and plasticity awarded by National Institutes of Health 2016 - 2025
- Transplant Infectious Diseases Interdisciplinary Research Training Grant (TIDIRTG) awarded by National Institutes of Health 2018 - 2023
- Regulation of the type 1 program during ILC3 plasticity awarded by National Institutes of Health 2020 - 2022
- Structural Biological Development of Fungal-Specific Calcineurin Inhibitors awarded by National Institutes of Health 2014 - 2021
- Molecular Mycology and Pathogenesis Training Program awarded by National Institutes of Health 2019 - 2021
- Regulatory Mechanisms of CD4+ T Cell Differentiation awarded by National Institutes of Health 2017 - 2021
- Organization and Function of Cellular Structure awarded by National Institutes of Health 1975 - 2020
- Network approach to dissecting genetic mediators of Multiple Sclerosis awarded by National Multiple Sclerosis Society 2015 - 2019
- Publications & Artistic Works
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Selected Publications
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Academic Articles
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Xu-Vanpala, Shengjie, M Elizabeth Deerhake, Joshua D. Wheaton, Morgan E. Parker, Praveen R. Juvvadi, Nancie MacIver, Maria Ciofani, and Mari L. Shinohara. “Functional heterogeneity of alveolar macrophage population based on expression of CXCL2.” Sci Immunol 5, no. 50 (August 7, 2020). https://doi.org/10.1126/sciimmunol.aba7350.Full Text Link to Item
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Ciofani, Maria. “Tγδ17 cells build up the nerve.” Nat Immunol 21, no. 4 (April 2020): 367–68. https://doi.org/10.1038/s41590-020-0642-4.Full Text Link to Item
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Parker, Morgan E., Alejandro Barrera, Joshua D. Wheaton, Matthew K. Zuberbuehler, David S. J. Allan, James R. Carlyle, Timothy E. Reddy, and Maria Ciofani. “c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program.” J Exp Med 217, no. 1 (January 6, 2020). https://doi.org/10.1084/jem.20191030.Full Text Link to Item
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Espinosa, Jaclyn R., Joshua D. Wheaton, and Maria Ciofani. “In Vitro Differentiation of CD4+ T Cell Effector and Regulatory Subsets.” Methods Mol Biol 2111 (2020): 79–89. https://doi.org/10.1007/978-1-0716-0266-9_7.Full Text Link to Item
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Parker, Morgan E., and Maria Ciofani. “Regulation of γδ T Cell Effector Diversification in the Thymus.” Front Immunol 11 (2020): 42. https://doi.org/10.3389/fimmu.2020.00042.Full Text Link to Item
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Wheaton, Joshua D., and Maria Ciofani. “JunB Controls Intestinal Effector Programs in Regulatory T Cells.” Frontiers in Immunology 11 (January 2020): 444. https://doi.org/10.3389/fimmu.2020.00444.Full Text
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Juvvadi, Praveen R., David Fox, Benjamin G. Bobay, Michael J. Hoy, Sophie M. C. Gobeil, Ronald A. Venters, Zanetta Chang, et al. “Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents.” Nat Commun 10, no. 1 (September 19, 2019): 4275. https://doi.org/10.1038/s41467-019-12199-1.Full Text Link to Item
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Wheaton, Joshua, and Maria Ciofani. “JunB controls intestinal effector programs in regulatory T cells,” September 16, 2019. https://doi.org/10.1101/772194.Full Text
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Zuberbuehler, Matthew K., Morgan E. Parker, Joshua D. Wheaton, Jaclyn R. Espinosa, Harmony R. Salzler, Eunchong Park, and Maria Ciofani. “Publisher Correction: The transcription factor c-Maf is essential for the commitment of IL-17-producing γδ T cells.” Nat Immunol 20, no. 5 (May 2019): 663. https://doi.org/10.1038/s41590-019-0349-6.Full Text Link to Item
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Miraldi, Emily R., Maria Pokrovskii, Aaron Watters, Dayanne M. Castro, Nicholas De Veaux, Jason A. Hall, June-Yong Lee, et al. “Leveraging chromatin accessibility for transcriptional regulatory network inference in T Helper 17 Cells.” Genome Res 29, no. 3 (March 2019): 449–63. https://doi.org/10.1101/gr.238253.118.Full Text Link to Item
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Zuberbuehler, Matthew K., Morgan E. Parker, Joshua D. Wheaton, Jaclyn R. Espinosa, Harmony R. Salzler, Eunchong Park, and Maria Ciofani. “The transcription factor c-Maf is essential for the commitment of IL-17-producing γδ T cells.” Nat Immunol 20, no. 1 (January 2019): 73–85. https://doi.org/10.1038/s41590-018-0274-0.Full Text Link to Item
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Wheaton, Joshua D., Chen-Hao Yeh, and Maria Ciofani. “Cutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt RORγt+ and Follicular Phenotypes.” J Immunol 199, no. 12 (December 15, 2017): 3931–36. https://doi.org/10.4049/jimmunol.1701134.Full Text Link to Item
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Carr, Tiffany M., Joshua D. Wheaton, Geoffrey M. Houtz, and Maria Ciofani. “JunB promotes Th17 cell identity and restrains alternative CD4+ T-cell programs during inflammation.” Nat Commun 8, no. 1 (August 21, 2017): 301. https://doi.org/10.1038/s41467-017-00380-3.Full Text Open Access Copy Link to Item
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Glasmacher, Elke, Smita Agrawal, Abraham B. Chang, Theresa L. Murphy, Wenwen Zeng, Bryan Vander Lugt, Aly A. Khan, et al. “A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes.” Science 338, no. 6109 (November 16, 2012): 975–80. https://doi.org/10.1126/science.1228309.Full Text Link to Item
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Ciofani, Maria, Aviv Madar, Carolina Galan, Maclean Sellars, Kieran Mace, Florencia Pauli, Ashish Agarwal, et al. “A validated regulatory network for Th17 cell specification.” Cell 151, no. 2 (October 12, 2012): 289–303. https://doi.org/10.1016/j.cell.2012.09.016.Full Text Link to Item
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Dervovic, Dzana D., Maria Ciofani, Korosh Kianizad, and Juan Carlos Zúñiga-Pflücker. “Comparative and functional evaluation of in vitro generated to ex vivo CD8 T cells.” J Immunol 189, no. 7 (October 1, 2012): 3411–20. https://doi.org/10.4049/jimmunol.1200979.Full Text Link to Item
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Kirigin, Francis F., Kenneth Lindstedt, Maclean Sellars, Maria Ciofani, Siao Li Low, Lachlan Jones, Fiona Bell, et al. “Dynamic microRNA gene transcription and processing during T cell development.” J Immunol 188, no. 7 (April 1, 2012): 3257–67. https://doi.org/10.4049/jimmunol.1103175.Full Text Link to Item
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Huh, Jun R., Monica W. L. Leung, Pengxiang Huang, Daniel A. Ryan, Michael R. Krout, Raghu R. V. Malapaka, Jonathan Chow, et al. “Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity.” Nature 472, no. 7344 (April 28, 2011): 486–90. https://doi.org/10.1038/nature09978.Full Text Link to Item
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Ciofani, Maria, and Juan Carlos Zúñiga-Pflücker. “Determining γδ versus αß T cell development.” Nat Rev Immunol 10, no. 9 (September 2010): 657–63. https://doi.org/10.1038/nri2820.Full Text Link to Item
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Chong, Mark M. W., Natalie Simpson, Maria Ciofani, Grace Chen, Amélie Collins, and Dan R. Littman. “Epigenetic propagation of CD4 expression is established by the Cd4 proximal enhancer in helper T cells.” Genes Dev 24, no. 7 (April 1, 2010): 659–69. https://doi.org/10.1101/gad.1901610.Full Text Link to Item
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Lauritsen, Jens Peter Holst, Gladys W. Wong, Sang-Yun Lee, Juliette M. Lefebvre, Maria Ciofani, Michele Rhodes, Dietmar J. Kappes, Juan Carlos Zúñiga-Pflücker, and David L. Wiest. “Marked induction of the helix-loop-helix protein Id3 promotes the gammadelta T cell fate and renders their functional maturation Notch independent.” Immunity 31, no. 4 (October 16, 2009): 565–75. https://doi.org/10.1016/j.immuni.2009.07.010.Full Text Link to Item
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Koltsova, Ekaterina K., Maria Ciofani, Robert Benezra, Toru Miyazaki, Neil Clipstone, Juan Carlos Zúñiga-Pflücker, and David L. Wiest. “Early growth response 1 and NF-ATc1 act in concert to promote thymocyte development beyond the beta-selection checkpoint.” J Immunol 179, no. 7 (October 1, 2007): 4694–4703. https://doi.org/10.4049/jimmunol.179.7.4694.Full Text Link to Item
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Palomero, Teresa, Maria Luisa Sulis, Maria Cortina, Pedro J. Real, Kelly Barnes, Maria Ciofani, Esther Caparros, et al. “Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia.” Nat Med 13, no. 10 (October 2007): 1203–10. https://doi.org/10.1038/nm1636.Full Text Link to Item
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Ciofani, Maria, and Juan Carlos Zúñiga-Pflücker. “The thymus as an inductive site for T lymphopoiesis.” Annu Rev Cell Dev Biol 23 (2007): 463–93. https://doi.org/10.1146/annurev.cellbio.23.090506.123547.Full Text Link to Item
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Ciofani, Maria, Gisèle C. Knowles, David L. Wiest, Harald von Boehmer, and Juan Carlos Zúñiga-Pflücker. “Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation.” Immunity 25, no. 1 (July 2006): 105–16. https://doi.org/10.1016/j.immuni.2006.05.010.Full Text Link to Item
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Zúñiga-Pflücker, Juan Carlos, and Maria Ciofani. “Pre-T cell receptor's clashing signals: "should I stay or should I go".” Immunity 24, no. 6 (June 2006): 669–70. https://doi.org/10.1016/j.immuni.2006.06.006.Full Text Link to Item
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Ciofani, Maria, and Juan Carlos Zúñiga-Pflücker. “A survival guide to early T cell development.” Immunol Res 34, no. 2 (2006): 117–32. https://doi.org/10.1385/IR:34:2:117.Full Text Link to Item
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Ciofani, Maria, and Juan Carlos Zúñiga-Pflücker. “Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism.” Nat Immunol 6, no. 9 (September 2005): 881–88. https://doi.org/10.1038/ni1234.Full Text Link to Item
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Schmitt, Thomas M., Maria Ciofani, Howard T. Petrie, and Juan Carlos Zúñiga-Pflücker. “Maintenance of T cell specification and differentiation requires recurrent notch receptor-ligand interactions.” J Exp Med 200, no. 4 (August 16, 2004): 469–79. https://doi.org/10.1084/jem.20040394.Full Text Link to Item
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Ciofani, Maria, Thomas M. Schmitt, Amelia Ciofani, Alison M. Michie, Nicolas Cuburu, Anne Aublin, Janet L. Maryanski, and Juan Carlos Zúñiga-Pflücker. “Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation.” J Immunol 172, no. 9 (May 1, 2004): 5230–39. https://doi.org/10.4049/jimmunol.172.9.5230.Full Text Link to Item
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Conference Papers
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Hoy, M. J., D. Fox, J. Wheaton, M. Mutz, W. J. Steinbach, M. Ciofani, and J. Heitman. “Novel FK506 analog exhibits anti-fungal activity against Cryptococcus neoformans in vitro and in an animal model.” In Medical Mycology, 56:S139–S139. OXFORD UNIV PRESS, 2018.Link to Item
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- Teaching & Mentoring
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Recent Courses
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